title: Blm10 binds to pre-activated proteasome core particles with open gate conformation.
abstract: Blm10 is bound to the yeast proteasome core particle, a crucial protease of eukaryotic cells [corrected]. Two gates, at both ends of the CP, control the access of protein substrates to the catalytic cavity of the CP. Normally, substrate access is auto-inhibited by a closed gate conformation unless regulatory complexes are bound to the CP and translocate protein substrates in an ATP-dependent manner. Here, we provide evidence that Blm10 recognizes pre-activated open gate CPs, which are assumed to exist in an equilibrium with inactive closed gate CP. Consequently, single-capped Blm10-CP shows peptide hydrolysis activity. Under conditions of disturbed CP assembly, as well as in open gate mutants, pre-activated CP or constitutively active CP, respectively, prevail. Then, Blm10 sequesters disordered and open gate CP by forming double-capped Blm10(2)-CP in which peptide hydrolysis activity is repressed. We conclude that Blm10 distinguishes between gate conformations and regulates the activation of CP.
authors.affiliation: Institute of Biochemistry, Charité-Universitätsmedizin Berlin, Monbijoustrasse 2, 10117 Berlin, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lehmann
authors.forename: Katharina
authors.initials: K
authors.lastname: Jechow
authors.forename: Cordula
authors.initials: C
authors.lastname: Enenkel
mesh_terms: D004789:Enzyme Activation; D004795:Enzyme Stability; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: C500597:Blm10 protein, S cerevisiae; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; C110856:proteasome maturation protein; D046988:Proteasome Endopeptidase Complex; C119011:26S proteasome non-ATPase regulatory subunit 13